Transcranial direct current stimulation to enhance cognition in euthymic bipolar disorder.

OBJECTIVES: To investigate the use of transcranial direct current stimulation (tDCS) for enhancing working memory and sustained attention in euthymic patients with bipolar disorder. METHODS: Fifteen patients with bipolar disorder received anodal left prefrontal tDCS with an extracephalic cathode (prefrontal condition), anodal left prefrontal and cathodal cerebellar tDCS (fronto-cerebellar condition), and sham tDCS given 'online' during performance on a working memory and sustained attention task in an intra-individual, cross-over, sham-controlled experimental design. Exploratory cluster analyses examined responders and non-responders for the different active tDCS conditions on both tasks. RESULTS: For working memory, approximately one-third of patients in both active tDCS conditions showed performance improvement. For sustained attention, three of 15 patients showed performance improvement with prefrontal tDCS. Responders to active tDCS for working memory performed more poorly on the task during sham tDCS compared to non-responders. CONCLUSIONS: A single session of active prefrontal or fronto-cerebellar tDCS failed to improve working memory or sustained attention performance in euthymic patients with bipolar disorder. Several important considerations are discussed in relation to future studies investigating tDCS for enhancing cognition in patients with bipolar disorder.

Pharmacological treatment approaches to difficult-to-treat depression.

In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial of almost 3000 patients with depression in the United States, 50% responded to the initial trial of a selective serotonin reuptake inhibitor antidepressant, but only a third achieved remission (nil or minimal depressive symptoms). The final remission rate, even after four potential treatment steps, was only 70%. This finding reflects the reality of clinical practice and highlights the need to employ the best available evidence in the management of people with complex depression. Before adopting a pharmacological strategy for a patient with difficult-to-treat depression, general clinical issues (such as missed psychiatric diagnoses, unresolved psychological issues and treatment non-adherence) should be considered. While there is no strong evidence for the order of implementing evidence-based pharmacological strategies for difficult-to-treat depression, we recommend: i) increase antidepressant dose; ii) switch to different antidepressant; iii) augment with a non-antidepressant agent; and iv) combine antidepressants. Sometimes it may be more appropriate to consider augmentation before switching antidepressants. The use of psychological interventions or other physical treatments such as electroconvulsive therapy should be considered at each step in management.

Augmenting transcranial direct current stimulation with (D)-cycloserine for depression: a pilot study.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that causes changes in cortical excitability. Recent double-blind placebo-controlled clinical trials suggest that tDCS may be efficacious in the treatment of depression. Pharmacological agents that prolong the effects of tDCS could lead to greater cumulative changes in cortical excitability, producing greater and more prolonged efficacy. One agent shown to prolong the excitability-enhancing effects of tDCS in healthy subjects is D-Cycloserine, a partial agonist at the glycine-binding site of N-methyl-D-aspartate receptors. We investigated whether combining prefrontal tDCS with D-Cycloserine could enhance and/or prolong the antidepressant effect of tDCS. METHODS: Five depressed subjects who had relapsed or failed to achieve remission after receiving a previous course of prefrontal tDCS were recruited. In this open-label pilot study, subjects ingested 100-mg D-Cycloserine 2 hours before tDCS sessions. Subjects received 20 minutes of tDCS at 2 mA on consecutive weekdays for a total of 20 sessions. The anode was placed at pF3 and the cathode at F8 (10/20 system). Clinical response was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: The change in Montgomery-Åsberg Depression Rating Scale scores was not greater with the combination of D-Cycloserine and tDCS than had previously been produced by tDCS alone. No significant additional adverse effects were reported. CONCLUSIONS: This pilot open-label study found that pretreatment with 100-mg D-Cycloserine 2 hours before tDCS was well tolerated but did not enhance the antidepressant efficacy of anodal prefrontal tDCS.

Correlates and outcomes of depressed out-patients with greater and fewer anxious symptoms: a CO-MED report.

The objective of this paper was to determine whether the presence of more vs. fewer anxious symptom features, at baseline, are associated with other clinical features and treatment outcomes in out-patients with major depressive disorder (MDD). This single-blind, randomized trial enrolled 665 MDD out-patients to compare the efficacy of two antidepressant medication combinations against escitalopram after 12-wk acute treatment and follow-up (total 28 wk). The sample was divided into those with greater (vs. fewer) anxiety features using the anxiety/somatization subscale of the baseline 17-item Hamilton Rating Scale for Depression. Baseline sociodemographic and clinical features, treatment features and outcomes compared these two groups. Overall, 74.7% of participants met the threshold for 'anxious features'. They were more likely to be female, have other concurrent anxiety disorders, more severe depression, more lethargic and melancholic features and poorer cognitive and physical functioning, quality of life and work and social adjustment. In acute treatment, participants with anxious features received comparatively higher doses of mirtazapine and venlafaxine and reported more side-effects. The groups with and without anxious features did not differ in treatment outcomes and side-effect burden. Despite being associated with a distinct clinical profile, baseline anxious features were not clinically useful in predicting acute treatment outcomes or differential treatment response.

Electroconvulsive practice in Singapore: a cross-sectional national survey.

INTRODUCTION: The use of electroconvulsive therapy (ECT) in Singapore dates back to 1947. However, there is little local information on the clinical practice of ECT and its standards. We aimed to conduct a comprehensive national survey of ECT practice in Singapore. METHODS: A cross-sectional structured questionnaire assessing the types of ECT (e.g. electrode placement, stimulus parameters), indications, anaesthetic technique, dosing methods, monitoring of outcomes and credentialing was sent in 2015 to all ECT centres in Singapore via email to collect qualitative and quantitative data regarding ECT. RESULTS: Data was obtained from all ECT centres (n = 6), which represented that ECT was available in 23.1% of all hospitals and 50.0% of all psychiatric specialist centres. The rate of ECT was 5.89 treatments per 10,000 residents per year, and each patient received an average of 5.4 ECT per course. Only 7.0% of ECT was administered for continuation/maintenance ECT. The most common indication for ECT was depression in 5 (83.3%) out of six centres, with schizophrenia being the second most common. In 5 (83.3%) out of six centres, ECT was brief (0.5 ms) bitemporal ECT with age-based dosing, and 93.0% of the sessions were conducted in an inpatient setting. All ECT was conducted under general anaesthesia, with propofol (66.7%) being the most common type of anaesthetic used. CONCLUSION: The practice of ECT in Singapore was highly uniform. The rates and indications for ECT were consistent with those of other developed countries, with greater use of ECT for schizophrenia. Future advances for ECT in Singapore include the use of individualised dosing based on empirical seizure threshold titration, expanded electrode placements and increased utilisation of continuation/maintenance ECT.

A cross-sectional study of burnout and its associations with learning environment and learner factors among psychiatry residents within a National Psychiatry Residency Programme.

BACKGROUND: Multiple studies have reported high burnout rates among residents, including psychiatry. There is a paucity of studies examining the relationship between burnout and learning context, stress levels, resilience, stigma in healthcare providers and coping methods concurrently within the same cohort. OBJECTIVE: We examined the rate of burnout among our psychiatry residents in a cross-sectional study and hypothesised that burnout is associated with poorer perception of learning environment, greater perceived stress, stigma levels, lower resilience and specific coping strategies during training. METHODS: Ninety-three out of 104 psychiatry residents (89.4%) within our National Psychiatry Residency Programme participated in the study from June 2016 to June 2018. Relevant scales were administered to assess the perception of learning environment, burnout, stress, resilience, stigma levels and coping methods, respectively. We performed comparisons of the above measures between groups (burnout vs no burnout) and within-group correlations for these same measures. RESULTS: Overall, 54.8% of the sample met criteria for burnout. Residents with burnout had poorer perception of the learning environment, greater stress levels (both p<0.001), were less willing to disclose/seek help and employed greater active-avoidance coping strategies. Within the burnout group, greater perceived stress was correlated with poorer perception of learning environment (rs=-0.549) and greater use of active-avoidance coping (rs=0.450) versus additional use of problem-focussed coping within the non-burnout group. CONCLUSIONS: Burnout was related to both environment and learner factors. These findings viewed within the transactional, sequential and imbalance models of burnout suggest the need to address stressors, beef up coping, provide continual support and develop resilience among our learners.

Cognitive complaints and predictors of perceived cognitive dysfunction in adults with major depressive disorder: Findings from the Cognitive Dysfunction in Asians with Depression (CogDAD) study.

BACKGROUND: Several studies have described the presence of perceived cognitive dysfunction amongst Asian patients with major depressive disorder (MDD). To date, no study has been conducted investigating the predictors of perceived cognitive dysfunction amongst Asian MDD patients. METHODS: This was a post-hoc analysis of the Cognitive Dysfunction in Asian patients with Depression (CogDAD) study. Descriptive statistics were used to describe the most common cognitive complaints by patients. Univariate and multivariate analyses were performed to determine variables associated with perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D). RESULTS: The CogDAD study population is comprised of MDD patients with mild-to-moderate depression (Patient Health Questionnaire 9-item [PHQ-9]: 11.3 ±â€¯6.9) who reported perceived cognitive dysfunction (PDQ-D = 22.6 ±â€¯16.2). The most common cognitive complaints were: mind drifting (42.3%), trouble making decision (39.6%) and trouble concentrating (38.0%). Predictors of perceived cognitive dysfunction were: being Southeast Asians (vs. Taiwanese) (p < 0.001), current episode longer than 8 weeks (vs. 1-8 weeks) (p < 0.05), the presence of disability (vs. no disability) (p < 0.05), younger age (p < 0.01), and higher PHQ-9 total scores (p < 0.001). LIMITATIONS: The causal relationship between predictive variables and PDQ-D could not be tested due to the cross-sectional nature of the study. Furthermore, a neuropsychological test was not included in the CogDAD study and use of concomitant medications, including anti-depressants, could have impacted patient's perceived cognitive ability. CONCLUSIONS: The present study results suggest a potential role for subjective cognitive assessment in patients with MDD who are young, with long durations of depression or severe depression.

Alcohol Use Disorders amongst Inpatients in a General Hospital in Singapore: Estimated Prevalence, Rates of Identification and Intervention.

INTRODUCTION: Many alcohol-related problems often go undetected and untreated. In Singapore, no epidemiological studies have been done in general hospitals on alcohol use disorders (AUD), i.e. alcohol dependence and abuse (DSM-IV-TR). Such findings are useful in planning AUD liaison services. In this study, we aim to estimate the prevalence of AUD among non-psychiatric inpatients and to determine the rates of identification and intervention rendered by medical staff. MATERIALS AND METHODS: Non-psychiatric medical and surgical wards inpatients aged 21 years and above were recruited over a 3-month period. The Alcohol Use Disorders Identification Test (AUDIT) was used to screen for AUD and the MINI International Neuropsychiatric Interview (MINI English Version 5.0.0) was administered to diagnose AUD if the AUDIT score was 8 or above. Case notes were independently reviewed for AUD identification and if interventions were offered during admissions. RESULTS: A total of 5599 inpatients were screened, of which 673 (12%) completed the screening using the AUDIT, and of these, 154 (2.8% of total sample) were positive for AUDIT. In this group, 107 were diagnosed with AUD. The estimated prevalence was 1.9% (approximately 400 cases per year per hospital). The medical staff identified only 25 (23.4%) cases of AUD, out of which, majority of them (76%) were rendered interventions. CONCLUSION: The rate of AUD identification by medical staff was low. Of those identified, majority were given interventions. Thus, the training of health care staff to identify AUD together with the implementation of brief interventions should be considered.

Thyroid Autoimmune Antibodies and Major Depressive Disorder in Women.

INTRODUCTION: Anti-thyroid antibodies are associated with extra-thyroid diseases such as Graves' ophthalmopathy and Hashimoto's encephalopathy. Some evidence suggests that anti-thyroid antibodies are also associated with depression. Interleukin (IL)-17 appears to play an important role in autoimmune thyroid disease. This study investigated whether specific thyroid autoantibodies and IL-17 distinguished persons with depression from non-depressed controls. MATERIALS AND METHODS: Forty-seven adult females with non-psychotic, current major depressive disorder and 80 healthy female controls participated in this study. Thyroid peroxidase antibodies, thyroglobulin antibodies, thyroid-stimulating hormone (TSH) receptor antibodies, free T3 and T4, TSH and IL-17 were measured from the serum. Measurements were repeated to assess test-retest reliability. Receiver operating characteristic (ROC) curves were used to estimate discriminatory values of the measurements. Differences between groups and associations between the clinical and biochemical assessments were analysed. RESULTS: Median TSH receptor antibody concentration was significantly higher in the depressed than control group (P <0.001). Area under the ROC curve was 0.80 (95% CI, 0.73 to 0.88). Higher TSH receptor antibody titres were associated with greater depression severity scores (r = 0.33, P <0.05). IL-17 levels were not associated with TSH receptor antibody levels or depression severity scores. Thyroid function and other thyroid autoantibodies were not associated with depression severity. CONCLUSION: TSH receptor antibodies might be a biomarker of immune dysfunction in depression.

Insomnia in the community.

Insomnia is the most common sleep complaint encountered in primary care. It affects both the individual and society through the burden of medical, psychiatric, interpersonal and social consequences. The management of patients affected by insomnia depends on the accurate diagnosis of the condition, consideration of the possible aetiologies, the duration of the insomnia and its impact on both the individual and society. Herein, we discuss the appropriate management of insomnia in the community.

Reduced inferior frontal gyrus activation during response inhibition to emotional stimuli in youth at high risk of bipolar disorder.

BACKGROUND: Functional brain imaging of young people at increased genetic risk for bipolar disorder provides a means of identifying potential endophenotypes for this condition. Dysfunctional neural mechanisms for the cognitive control of emotion are implicated in the genetic predisposition to bipolar disorder, with aberrant activity in frontocortical, striatal, and limbic brain regions previously reported in subjects with established bipolar disorder during inhibitory and emotion processing tasks. METHODS: Functional brain activity during inhibition of emotional material in young people at increased genetic risk for bipolar disorder was investigated using a facial-emotion go/no-go task during functional magnetic resonance imaging. Data from 47 genetically high-risk individuals aged 18 to 30 years with at least one first-degree relative with bipolar disorder were compared with 49 control subjects (within the same age range but without a family history of bipolar disorder or other severe mental illness). RESULTS: Whole-brain corrected analyses revealed a highly specific and significant lack of recruitment of the inferior frontal gyrus when inhibiting responses to fearful faces in the high-risk participants compared with control subjects (p = .011, family-wise error, peak voxel). CONCLUSIONS: Impaired inhibitory function of the inferior frontal cortex may represent a trait marker of vulnerability to bipolar disorder. That this finding was revealed during inhibition of emotional material further implicates dysregulated frontolimbic brain networks as a potential neurocognitive endophenotype for bipolar disorder and provides evidence for pre-existing functional disturbances in those at high genetic risk for bipolar disorder.

Use of antidepressants in the treatment of chronic pain.

There is a high prevalence of chronic pain disorders in the population and the individual and societal costs are large. Antidepressants have been used in the treatment of chronic pain and the pain-relieving effects are independent of the mood-elevating properties. We reviewed randomised-controlled trials, systematic reviews and meta-analyses of antidepressants in the treatment of chronic pain disorders which were identified through searches of MEDLINE and EMBASE. Antidepressants have proved to be effective in the treatment of fibromyalgia, chronic low back pain, diabetic neuropathy, postherpetic neuralgia and chronic headache, in particular tricyclic antidepressants (TCAs). There is emerging evidence that newer dual-action antidepressants are equally efficacious. Antidepressants provide a viable option in the management of chronic pain disorders. Further research into novel antidepressants will aid the pain clinician in optimising treatment for patients.